What I'd like to do is just drag us all down into the gutter, and actually all the way down into the sewer because I want to talk about diarrhea. And in particular, I want to talk about the design of diarrhea. And when evolutionary biologists talk about design, they really mean design by natural selection. And that brings me to the title of the talk, "Using Evolution to Design Disease Organisms Intelligently." And I also have a little bit of a sort of smartass subtitle to this. But I'm not just doing this to be cute. I really think that this subtitle explains what somebody like me, who's sort of a Darwin wannabe, how they actually look at one's role in sort of coming into this field of health sciences and medicine. It's really not a very friendly field for evolutionary biologists. You actually see a great potential, but you see a lot of people who are sort of defending their turf, and may actually be very resistant, when one tries to introduce ideas.
我想要做的就是把大家都拖到排水溝裡, 其實是一路滑下到下水道, 因為我想談的是有關於腹瀉。 更具體而言,我想談談 腹瀉的設計圖譜 當生物進化學家們談論設計時 真正指的是經由自然選擇的設計, 這也就是我的演講標題 “聰明巧妙的使用生物進化去設計病菌." 我也有加上有一點自負的副標題, 但這樣做不是要譁眾取寵. 我真的認為這副標題幫這些像我一樣 想要成為達爾文第二的人闡述了心聲 表達他們是如何真正看待自己 在健康科學和醫學領域裡的角色。 對進化生物學家來說這實在不是一個很友好的領域。 雖然具有強大潛力, 但你也會看到很多人固步自封, 有時當試圖引進這些想法時 會被強烈排斥。
So, all of the talk today is going to deal with two general questions. One is that, why are some disease organisms more harmful? And a very closely related question, which is, how can we take control of this situation once we understand the answer to the first question? How can we make the harmful organisms more mild? And I'm going to be talking, to begin with, as I said, about diarrheal disease organisms. And the focus when I'm talking about the diarrheal organisms, as well as the focus when I'm talking about any organisms that cause acute infectious disease, is to think about the problem from a germ's point of view, germ's-eye view. And in particular, to think about a fundamental idea which I think makes sense out of a tremendous amount of variation in the harmfulness of disease organisms. And that idea is that from the germ's-eye point of view, disease organisms have to get from one host to another, and often they have to rely on the well-being of the host to move them to another host.
今天演講的主題是要針對兩個很普通的問題. 一個是,為什麼有些病菌比較有殺傷力 而一個非常密切相關的問題是: 一旦我們知道第一個問題的答案後, 我們如何才能控制這種情況? 如何使殺傷力強的病菌變成比較溫和呢? 而我將討論的,正如我所說, 首先關於腹瀉疾病的病菌。 我的焦點不僅僅是討論各種腹瀉的病菌 而且還包括當談論任何病菌 造成急性傳染病時 用病菌的角度來思考問題. 病菌的觀點. 用這方法來思考探究一個根本的想法, 我覺得很合理, 尤其是面對殺傷力強 且具有大量變異性的病源體時. 從細菌的角度來看世界, 通常病菌必須從一個宿主轉移到另一個宿主, 他們往往必需要依靠還算健康的宿主 來傳染疾病到另一個宿主.
But not always. Sometimes, you get disease organisms that don't rely on host mobility at all for transmission. And when you have that, then evolutionary theory tells us that natural selection will favor the more exploitative, more predator-like organisms. So, natural selection will favor organisms that are more likely to cause damage. If instead transmission to another host requires host mobility, then we expect that the winners of the competition will be the milder organisms. So, if the pathogen doesn't need the host to be healthy and active, and actual selection favors pathogens that take advantage of those hosts, the winners in the competition are those that exploit the hosts for their own reproductive success. But if the host needs to be mobile in order to transmit the pathogen, then it's the benign ones that tend to be the winners.
但並非總是如此。 有時候,讓人得到疾病的病源體 不依賴宿主的活動力來傳播疾病。 這情形下,進化理論告訴我們, 自然選擇將有利於比較兇猛, 更具侵略性的病源體, 也就是自然選擇將有利 於殺傷力強的病源體, 相反的,如果需要依賴宿主的活動性來傳播疾病, 我們可以預料競爭中的贏家 將是溫和的菌種. 所以,如果病源體不需要健康活動的宿主來傳播疾病, 那實際上自然選擇的病源體, 是有利於會佔盡宿主的便宜,摧殘宿主的菌種, 所以競爭中的贏家是那些剝削宿主 來繁殖自己的病源體. 但是,如果需要宿主的活動力來傳播疾病 那麼那些較溫和的病源體,往往會成為贏家.
So, I'm going to begin by applying this idea to diarrheal diseases. Diarrheal disease organisms get transmitted in basically three ways. They can be transmitted from person-to-person contact, person-to-food-then-to-person contact, when somebody eats contaminated food, or they can be transmitted through the water. And when they're transmitted through the water, unlike the first two modes of transmission, these pathogens don't rely on a healthy host for transmission. A person can be sick in bed and still infect tens, even hundreds of other individuals. To sort of illustrate that, this diagram emphasizes that if you've got a sick person in bed, somebody's going to be taking out the contaminated materials. They're going to wash those contaminated materials, and then the water may move into sources of drinking water. People will come in to those places where you've got contaminated drinking water, bring things back to the family, may drink right at that point. The whole point is that a person who can't move can still infect many other individuals.
所以我將開始應用這一想法到腹瀉的疾病上。 腹瀉的病菌基本是以三種方式傳播。 它們可以由人接觸傳染到另一人, (人-食物-人) 人吃下被污染的食物而傳染 或者通過水傳播。(水媒) 如果通過水傳播, 那就不像前兩種模式傳染, 這些病源體不依賴於一個健康的宿主傳播病源體。 一個人可以是重病在床,仍然感染其他人, 甚至數百個人。 這附圖可說明更清楚,這圖強調, 如果有一個生病的人在床上, 有人需要處理被污染的器皿, 他們將清洗這些受污染的器具. 然後髒水可能進入飲用水源中, 人們會去在那些地方取水, 而這些是被污染的飲用水. 他們會把水帶回家, 有時就在水源處喝上幾口. 整個的重點是:一個人即使沒有活動力 仍然可以感染許多其他個人。
And so, the theory tells us that when diarrheal disease organisms are transported by water, we expect them to be more predator-like, more harmful. And you can test these ideas. So, one way you can test is just look at all diarrheal bacteria, and see whether or not the ones that tend to be more transmitted by water, tend to be more harmful. And the answer is -- yep, they are. Now I put those names in there just for the bacteria buffs, but the main point here is that -- (Laughter) there's a lot of them here, I can tell -- the main point here is that those data points all show a very strong, positive association between the degree to which a disease organism is transmitted by water, and how harmful they are, how much death they cause per untreated infection. So this suggests we're on the right track. But this, to me, suggests that we really need to ask some additional questions.
所以,理論告訴我們, 當腹瀉的病菌是經由水傳播, 我們可預料病源體更凶狠,更有害的。 而且,您可以測試這些推論。 只需看看所有腹瀉細菌們, 看是否那些更趨向於利用水傳播 的病源體,往往更有殺傷力? 答案是-沒錯,它們是。 現在我為細菌迷把很多病菌名字列在此, 但主要的一點是 - (眾笑) 我敢說,這裡很多是細菌迷- 重點是,這些數據點 均表現出非常強烈的正向關聯: 越是依賴水傳播疾病的病菌, 殺傷力越強. 以及如果未經治療的死亡率. 因此,這表示我們的推論是正確的, 我建議我們真的需要 深入探討這現象.
Remember the second question that I raised at the outset was, how can we use this knowledge to make disease organisms evolve to be mild? Now, this suggests that if you could just block waterborne transmission, you could cause disease organisms to shift from the right-hand side of that graph to the left-hand side of the graph. But it doesn't tell you how long. I mean, if this would require thousands of years, then it's worthless in terms of controlling of these pathogens. But if it could occur in just a few years, then it might be a very important way to control some of the nasty problems that we haven't been able to control. In other words, this suggests that we could domesticate these organisms. We could make them evolve to be not so harmful to us.
記得我在一開始就提出了的第2個問題嗎: 我們如何用這些知識, 使病源體進化成較溫和的細菌呢? 所以現在假設如果你能阻止水媒傳播, 那表明就能把這種細菌們的 進化從圖中的右邊推向到左邊去. 但是我們不知要多久,進化才能完成. 我的意思是,如果這將需要數千年, 那不值得去試控制這些病源體。 但如果它可能發生在短短幾年內, 那麼它可能是一個非常重要的方式,來控制 那些我們以前沒法控制,難纏困難的問題. 換言之,這表明我們可以 馴養這些細菌們, 使他們進化成較溫和的細菌.
And so, as I was thinking about this, I focused on this organism, which is the El Tor biotype of the organism called Vibrio cholerae. And that is the species of organism that is responsible for causing cholera. And the reason I thought this is a really great organism to look at is that we understand why it's so harmful. It's harmful because it produces a toxin, and that toxin is released when the organism gets into our intestinal tract. It causes fluid to flow from the cells that line our intestine into the lumen, the internal chamber of our intestine, and then that fluid goes the only way it can, which is out the other end. And it flushes out thousands of different other competitors that would otherwise make life difficult for the Vibrios.
所以,當我在作研究時我把重心放在這個EL Tor(埃爾托) 生物型的細菌上,也就是被稱為霍亂弧菌的菌種. 這種病源體是造成 霍亂的原因。 而我之所以認為研究這菌種是很棒的題材, 是因為我們已知道它為什麼如此有殺傷力。 它的有害,是因為它會產生一種毒素. 當霍亂弧菌進入我們的腸道的時候, 毒素會被釋放出來. 這會使體液從腸壁細胞流入腸道(腔)中 --就是腸子中間的內在管腔. 然後,這液體流向唯一可去的另一端,排出人體外. 經由這過程沖刷走數以千計不同種腸道內競爭菌種, 使霍亂弧菌可以容易生存繁殖下來.
So what happens, if you've got an organism, it produces a lot of toxin. After a few days of infection you end up having -- the fecal material really isn't so disgusting as we might imagine. It's sort of cloudy water. And if you took a drop of that water, you might find a million diarrheal organisms. If the organism produced a lot of toxin, you might find 10 million, or 100 million. If it didn't produce a lot of this toxin, then you might find a smaller number. So the task is to try to figure out how to determine whether or not you could get an organism like this to evolve towards mildness by blocking waterborne transmission, thereby allowing the organism only to be transmitted by person-to-person contact, or person-food-person contact -- both of which would really require that people be mobile and fairly healthy for transmission.
然後呢?如果有一種病源體在體內, 它產生大量的毒素. 經過幾天後最終的結果是-- 糞便排洩物並不像我們想的那麼噁心. 只是一灘混濁的水. 如果你從中取一滴的水, 你會發現一百萬腹瀉病源體在其中. 如果病源體產生了大量的毒素, 你可能會找到1千萬或1億個病源體. 但如果病源體沒有產生了大量的毒素, 可能只會被發現較少量的病源體. 因此,主要的任務是設法弄清楚 如何能確定是否經由阻斷它們的水媒介傳播途徑, 可以使這種殺傷力強的病源體進化成較溫和的病源體 從而使傳播途徑只有 人對人直接接觸, 或人-食物-人的接觸感染. 而此二種都是需要有 足夠活動力或還算健康的人來傳播.
Now, I can think of some possible experiments. One would be to take a lot of different strains of this organism -- some that produce a lot of toxins, some that produce a little -- and take those strains and spew them out in different countries. Some countries that might have clean water supplies, so that you can't get waterborne transmission: you expect the organism to evolve to mildness there. Other countries, in which you've got a lot of waterborne transmission, there you expect these organisms to evolve towards a high level of harmfulness, right? There's a little ethical problem in this experiment. I was hoping to hear a few gasps at least. That makes me worry a little bit.
於是,我能想到一些可能的實驗。 其中之一是採取了很多同種病菌的不同菌株(不同亞型) 一些會產生大量的毒素,一些只產生少數的毒素- 把這些不同菌株,散播在不同的國家。 有些國家有清潔食水供應 所以不能利用水來傳播, 您可以預期在那裡病菌的進化會更溫和。 但有些國家,有很多水媒傳播機會, 所以你預期這些病菌的生物進化, 會邁向更有殺傷力的方向,對不對? 這實驗會面臨一個道德問題。 我以為會聽到一些人(驚嚇的)倒抽一口氣。 這就會使我有點擔心。
(Laughter)
笑聲
But anyhow, the laughter makes me feel a little bit better. And this ethical problem's a big problem. Just to emphasize this, this is what we're really talking about. Here's a girl who's almost dead. She got rehydration therapy, she perked up, within a few days she was looking like a completely different person. So, we don't want to run an experiment like that. But interestingly, just that thing happened in 1991. In 1991, this cholera organism got into Lima, Peru, and within two months it had spread to the neighboring areas. Now, I don't know how that happened, and I didn't have anything to do with it, I promise you. I don't think anybody knows, but I'm not averse to, once that's happened, to see whether or not the prediction that we would make, that I did make before, actually holds up. Did the organism evolve to mildness in a place like Chile, which has some of the most well protected water supplies in Latin America? And did it evolve to be more harmful in a place like Ecuador, which has some of the least well protected? And Peru's got something sort of in between.
不過,無論如何,笑聲讓我覺得好一點。 而這種道德問題是一個大問題。 為了強調這一點,也這就是我們真正談論的。 看這女孩差一點死了。 她得到了支持性補充體液療法,才恢復起來, 幾天之內,她看上去像一個完全不同的人。 因此,我們不希望進行這樣的實驗。 但有意思的是,類似的狀況發生在1991年。 1991年,霍亂病菌侵襲秘魯首都利馬, 並在兩個月內,蔓延到鄰近地區(國家)。 即使是現在我也不知道為什麼發生那瘟疫, 我向你們保證,那跟我沒有任何關係。 我不認為有人知道為什麼會發生, 一旦這發生了,我不反對, 借由這機會來分析看看是否我們的推論是對的, 就是我曾經提出過的理論,是否經得起考驗。 在智利是否霍亂病菌進化成較溫和的菌種, 因為智利在拉丁美洲具有最為完善的 水源保護系統? 是否在厄瓜多爾霍亂病菌進化成殺傷力更強的菌種 因為厄瓜多爾的水源最不受保護? 而秘魯對水源的保護程度是介在兩國之間.
And so, with funding from the Bosack-Kruger Foundation, I got a lot of strains from these different countries and we measured their toxin production in the lab. And we found that in Chile -- within two months of the invasion of Peru you had strains entering Chile -- and when you look at those strains, in the very far left-hand side of this graph, you see a lot of variation in the toxin production. Each dot corresponds to an islet from a different person -- a lot of variation on which natural selection can act. But the interesting point is, if you look over the 1990s, within a few years the organisms evolved to be more mild. They evolved to produce less toxin. And to just give you a sense of how important this might be, if we look in 1995, we find that there's only one case of cholera, on average, reported from Chile every two years.
因為有Bozack-Kruger基金會的財政協助, 我們從這些國家得到了很多不同的菌株.(樣品) 我們於是在實驗室測量它們產生的毒素. 我們發現,在智利-霍亂入侵秘魯兩個月後, 霍亂病菌漫延入智利. 仔細研究這些菌株(種), 在這個圖的最左邊, 毒素的生產量有很大的變異性(很多不同的菌株) 每個點或一個島形代表來自不同的個人 自然選擇可以倒導致很多變化. 但有趣的一點是,如果你看整個1990年代, 在幾年內霍亂病菌進化成較溫和的菌種. 它們發展成只會產生少量毒素的菌種. 更清楚的讓你們瞭解這個的重要性, 如果研究1995年只有一個霍亂病例, 平均每二年只有一個霍亂病例.
So, it's controlled. That's how much we have in America, cholera that's acquired endemically, and we don't think we've got a problem here. They didn't -- they solved the problem in Chile. But, before we get too confident, we'd better look at some of those other countries, and make sure that this organism doesn't just always evolve toward mildness. Well, in Peru it didn't. And in Ecuador -- remember, this is the place where it has the highest potential waterborne transmission -- it looked like it got more harmful. In every case there's a lot of variation, but something about the environment the people are living in, and I think the only realistic explanation is that it's the degree of waterborne transmission, favored the harmful strains in one place, and mild strains in another.
所以,霍亂被控制住了. 這跟在美國發生律一樣. 霍亂是一種區域性的瘟疫. 我不認為在美國我們有霍亂瘟疫的問題. 它們不是問題--在智利他們解決了這個瘟疫問題. 但在我們過於自信前,我們最好看看其他的鄰近國家. 並確認這些病菌(不是)只朝著更溫和的方向進化. 嗯,在秘魯病菌就不是變溫和。 而在厄瓜多爾-記得嗎這地方的 水媒傳輸可能性最高- -看起來病菌進化得更有殺傷力. 每個例子都有很多變異性, 這是與人們居住的環境有關. 我認為唯一真正的解釋是在於 病菌水媒傳輸的程度. 所以有些地區進化成殺傷力強的菌種.有些則進化成溫和菌種.
So, this is very encouraging, it suggests that something that we might want to do anyhow, if we had enough money, could actually give us a much bigger bang for the buck. It would make these organisms evolve to mildness, so that even though people might be getting infected, they'd be infected with mild strains. It wouldn't be causing severe disease. But there's another really interesting aspect of this, and this is that if you could control the evolution of virulence, evolution of harmfulness, then you should be able to control antibiotic resistance. And the idea is very simple. If you've got a harmful organism, a high proportion of the people are going to be symptomatic, a high proportion of the people are going to be going to get antibiotics. You've got a lot of pressure favoring antibiotic resistance, so you get increased virulence leading to the evolution of increased antibiotic resistance. And once you get increased antibiotic resistance, the antibiotics aren't knocking out the harmful strains anymore. So, you've got a higher level of virulence.
因此,這結果非常令人興奮, 這代表有些事我們應該去做, 如果我們有足夠的錢,我們可更有效率的利用這錢來(控制瘟疫) 使這些病菌進化成溫和菌種. 所以,即使人們可能被感染, 他們只會被溫和的菌種(株)感染 不會引起嚴重的症狀. 還有更有意思的另方面是: 如果我們可以控制病毒性的演變, 危害性的進化. 那我們應該能夠控制抗生素的耐藥性 原理非常簡單, 如果人們被殺傷力強的菌種感染, 就會有高比例的人生病(症狀嚴重). 那大量抗生素將會被使用來控制病情, 結果會有利於抗生素耐藥性的產生. 也就是增加導致毒性更強 且對抗生素產生耐藥性的細菌增加. 一旦耐藥性增強, 這種抗生素就不再對這菌種(株)產生作用. 那細菌的毒性會更強.
So, you get this vicious cycle. The goal is to turn this around. If you could cause an evolutionary decrease in virulence by cleaning up the water supply, you should be able to get an evolutionary decrease in antibiotic resistance. So, we can go to the same countries and look and see. Did Chile avoid the problem of antibiotic resistance, whereas did Ecuador actually have the beginnings of the problem? If we look in the beginning of the 1990s, we see, again, a lot of variation. In this case, on the Y-axis, we've just got a measure of antibiotic sensitivity -- and I won't go into that. But we've got a lot of variation in antibiotic sensitivity in Chile, Peru and Ecuador, and no trend across the years. But if we look at the end of the 1990s, just half a decade later, we see that in Ecuador they started having a resistance problem. Antibiotic sensitivity was going down. And in Chile, you still had antibiotic sensitivity.
最後這是個惡性循環. 我們的目標是要扭轉這個局面。 如果可以通過淨化水源來 進化下降細菌病毒性 那麼也應該經由此進化減少 抗生素的耐藥性. 因此,讓我們再一次仔細研究這三個相同國家. 到底智利有沒有避免抗生素產生耐藥性的問題? 而相對的厄瓜多爾實際上有沒有發生耐藥性的問題? 如果我們比較90年代的初期, 我們會發現到很多變異性,(三個國家結果相似)。 在此,Y軸代表病菌對抗生素的敏感性, 我不打算深入探討下去. 在智利,秘魯和厄瓜多爾病菌對抗生素的敏感性(有效性)的差異性變化很大. (有些菌種對抗生素很敏感;有些不敏感).我們沒有接下去幾年的記錄數據. 但是如果我們看看90年代末期,短短五年而已, 在厄瓜多爾已經開始有抗藥性的問題。 抗生素的敏感性一直在下降. 在智利抗生素依然保持其敏感性.
So, it looks like Chile dodged two bullets. They got the organism to evolve to mildness, and they got no development of antibiotic resistance. Now, these ideas should apply across the board, as long as you can figure out why some organisms evolved to virulence. And I want to give you just one more example, because we've talked a little bit about malaria. And the example I want to deal with is, or the idea I want to deal with, the question is, what can we do to try to get the malarial organism to evolve to mildness? Now, malaria's transmitted by a mosquito, and normally if you're infected with malaria, and you're feeling sick, it makes it even easier for the mosquito to bite you.
因此,可以說智利躲過兩個難題: (霍亂)病菌進化成溫和菌種, 而且他們依然保持抗生素的敏感性. 這種理論應該被大量採用, 只要我們弄清楚為什麼有些病菌會進化到更具毒性. 我想再給你另一個例子瘧疾. 因為我們已經談了一點有關於瘧疾的疾病。 而有關這例子我想表達的是, 我的想法是,問題是, 我們該如何做能使瘧疾進化溫和呢? 瘧疾是由蚊子傳播的, 通常狀況下如果感染了瘧疾,人會覺得不舒服虛弱, 所以更容易被蚊子咬。
And you can show, just by looking at data from literature, that vector-borne diseases are more harmful than non-vector-borne diseases. But I think there's a really fascinating example of what one can do experimentally to try to actually demonstrate this. In the case of waterborne transmission, we'd like to clean up the water supplies, see whether or not we can get those organisms to evolve towards mildness. In the case of malaria, what we'd like to do is mosquito-proof houses. And the logic's a little more subtle here. If you mosquito-proof houses, when people get sick, they're sitting in bed -- or in mosquito-proof hospitals, they're sitting in a hospital bed -- and the mosquitoes can't get to them.
只要看看文獻資料,即可以知道, 需要媒介傳播的疾病比無需媒介傳播 的疾病更有殺傷力. 但我認為這是一個非常有趣的例子, 來實際實驗證明我們的理論. 在這水媒傳播疾病例子, 我們把水源淨化控制, 看看是否能不能讓這些病菌進化成更溫和。 但對瘧疾而言,我們想要做的是建防蚊房. 邏輯推理上更微妙. 如果有人得到瘧疾,就把 他們擱置在防蚊子的房子裡的床上, 或防蚊子的醫院床上. 蚊子就無法叮他們了.
So, if you're a harmful variant in a place where you've got mosquito-proof housing, then you're a loser. The only pathogens that get transmitted are the ones that are infecting people that feel healthy enough to walk outside and get mosquito bites. So, if you were to mosquito proof houses, you should be able to get these organisms to evolve to mildness. And there's a really wonderful experiment that was done that suggests that we really should go ahead and do this. And that experiment was done in Northern Alabama. Just to give you a little perspective on this, I've given you a star at the intellectual center of the United States, which is right there in Louisville, Kentucky. And this really cool experiment was done about 200 miles south of there, in Northern Alabama, by the Tennessee Valley Authority. They had dammed up the Tennessee River. They'd caused the water to back up, they needed electric, hydroelectric power. And when you get stagnant water, you get mosquitoes. They found in the late '30s -- 10 years after they'd made these dams -- that the people in Northern Alabama were infected with malaria, about a third to half of them were infected with malaria.
因此,如果你是一個殺傷力強的細菌變種, 卻被防蚊子的房子關起來,沒蚊子,那麼你注定是一個失敗者。 唯一能傳播的病菌(變種)是那些被感染的人 還有足夠的活力在外面趴趴走, 然後才有機會被蚊蟲叮咬來傳播病菌. 因此,如果利用防蚊子的房子, 我們應該能夠迫使這瘧疾細菌進化成溫和菌種. 從以下這個完美實驗的結果顯示出: 我們真的應該繼續這樣做。 那個實驗是在阿拉巴馬州北部實行. 為了給你更具體的認知, 我在美國的知識中心,肯塔基州的路易斯維爾, 畫一個星星"*". 在那地區大約200英里以南完成這麼酷的實驗. 也就是阿拉巴馬州北部, 由於田納西河流域管理局 在田納西河建水庫, 阻斷了水流. 他們需要電,用水來發電. 水庫的積水是死水,所以會滋生蚊子. 這是在1930年代末期-- 即是建水壩後的10年後- 在阿拉巴馬北部瘧疾開始傳播. 大約有三分之一到一半的居民人被感染了瘧疾。
This shows you the positions of some of these dams. OK, so the Tennessee Valley Authority was in a little bit of a bind. There wasn't DDT, there wasn't chloroquines: what do they do? Well, they decided to mosquito proof every house in Northern Alabama. So they did. They divided Northern Alabama into 11 zones, and within three years, about 100 dollars per house, they mosquito proofed every house. And these are the data. Every row across here represents one of those 11 zones. And the asterisks represent the time at which the mosquito proofing was complete. And so what you can see is that just the mosquito-proofed housing, and nothing else, caused the eradication of malaria. And this was, incidentally, published in 1949, in the leading textbook of malaria, called "Boyd's Malariology." But almost no malaria experts even know it exists. This is important, because it tells us that if you have moderate biting densities, you can eradicate malaria by mosquito proofing houses.
這圖標示這些水壩的位置. 不錯!那時田納西河流域管理局是面臨一些困境. 那時沒有DDT(農業),沒有氯奎因(治瘧疾藥) 那他們能做什麼? 於是他們決定使北阿拉巴馬州家家戶戶都能防蚊. 他們就這樣做.把北阿拉巴馬州分11個區, 並在三年內,每家約只用 100美元, 家家戶戶都有防蚊設備 這些都是當時的數據證明. 豎立的每一行各代表這不同的11區。 這裡星(*)號代表在何時 在這些區完成防蚊設備. 你可以看到的是只有 家家戶戶完成防蚊設備.沒有別的, 就這樣根除瘧疾。 整個瘟疫只在1949年最具領導地位的 教科書"Boyd瘧疾病理學"中,曾被順便一提過. 幾乎沒有任何瘧疾病理專家知道它的存在過. 這一點很重要, 因為它告訴我們如果在中度機率被蚊子叮咬的地區, 只要具備防蚊設備就可以根除瘧疾.
Now, I would suggest that you could do this in a lot of places. Like, you know, just as you get into the malaria zone, sub-Saharan Africa. But as you move to really intense biting rate areas, like Nigeria, you're certainly not going to eradicate. But that's when you should be favoring evolution towards mildness. So to me, it's an experiment that's waiting to happen, and if it confirms the prediction, then we should have a very powerful tool. In a way, much more powerful than the kind of tools we're looking at, because most of what's being done today is to rely on things like anti-malarial drugs. And we know that, although it's great to make those anti-malarial drugs available at really low cost and high frequency, we know that when you make them highly available you're going to get resistance to those drugs. And so it's a short-term solution. This is a long-term solution.
所以現在,我建議這方法可被應用在很多地區. 比如,大家都知的,一些瘧疾區, 如非洲撒哈拉以南的地區. 但是如果到被蚊子叮很高機率的區域,像奈及利亞. 這招行不通,瘧疾無法根除. 可是經由這樣應能有利於讓病菌進化成溫和菌種. 對我來說,我期待它的發生. 如果結果是如我們所預期的, 那麼我們就應該有一個非常有利的工具(方法)。 在某種程度上,這是比我們現在使用的方法更得力. 因為現在我們所做的大多是 依賴抗瘧疾藥物去控制瘧疾. .儘管藥物現在很便宜很容易取得, 被大量使用, 但我們都知道當藥物被高頻率使用, 那就更容易產生抗藥性而失效. 所以使用藥物控制(瘟疫)只是暫時的解決方案. (進化成溫和菌種)這才是長期一勞永逸的方法.
What I'm suggesting here is that we could get evolution working in the direction we want it to go, rather than always having to battle evolution as a problem that stymies our efforts to control the pathogen, for example with anti-malarial drugs. So, this table I've given just to emphasize that I've only talked about two examples. But as I said earlier, this kind of logic applies across the board for infectious diseases, and it ought to. Because when we're dealing with infectious diseases, we're dealing with living systems. We're dealing with living systems; we're dealing with systems that evolve. And so if you do something with those systems, they're going to evolve one way or another. And all I'm saying is that we need to figure out how they'll evolve, so that -- we need to adjust our interventions to get the most bang for the intervention buck, so that we can get these organisms to evolve in the direction we want them to go.
我的建議是我們可以左右細菌進化 使它們向我們希望的方向前進. 而不是總是跟細菌進化鬥爭和 這阻礙我們控制病源體的努力成效 比如說抗瘧疾藥物使細菌進化更毒 這個圖表只是要強調, 雖然我只談到兩個例子. 但正如我剛才所說,這種邏輯適用於 所有傳染性疾病,而且這是應該要做的. 因為當我們面對處理傳染性疾病時,我們面對的是一個生命系統, 當面對的是一個生命系統,時 生命系統會進化。 所以如果人為對這系統做些干預, 它不是進化成溫和,就是成殺傷力更強的. 所有我要強調的是,我們需要弄清楚它們會如何進化, 然後我們可以調整我們的干預措施, 得到最大的利益. 使這些細菌朝我們希望它們進化的方向前去.
So, I don't really have time to talk about those things, but I did want to put them up there, just to give you a sense that there really are solutions to controlling the evolution of harmfulness of some of the nasty pathogens that we're confronted with. And this links up with a lot of the other ideas that have been talked about. So, for example, earlier today there was discussion of, how do you really lower sexual transmission of HIV? What this emphasizes is that we need to figure out how it will work. Will it maybe get lowered if we alter the economy of the area? It may get lowered if we intervene in ways that encourage people to stay more faithful to partners, and so on.
我並沒有時間來更深入談論這些事, 我這麼做是希望引起大家的注意力 給你們一些更貼切的感覺,我們確實有辦法. 可以控制我們現在所面臨的 一些難纏有害的病菌的進化過程. 這其實與許多已經講過了其他的想法貫通. 舉例來說,今天早些時候有討論過的 如何能真的降低性病愛滋病的傳染? 重點是我們需要弄清楚我們該如何做才會有效. 是不是改變這地區的經濟狀況就可降低愛滋病的得病率? 如果經由鼓勵人們對性伴侶的 忠誠度是否得病率會降低?等等方法.
But the key thing is to figure out how to lower it, because if we lower it, we'll get an evolutionary change in the virus. And the data really do support this: that you actually do get the virus evolving towards mildness. And that will just add to the effectiveness of our control efforts. So the other thing I really like about this, besides the fact that it brings a whole new dimension into the study of control of disease, is that often the kinds of interventions that you want, that it indicates should be done, are the kinds of interventions that people want anyhow. But people just haven't been able to justify the cost.
但最主要的關鍵是要弄清楚如何降低愛滋病的傳染率, 因為如果我們能降低傳染率,我們可以促使病毒進化改變. 數據確實支持這一點: 我們確實使病毒不斷進化成溫和的病毒. 這會使我們的控制方法更有效. 另一個讓我喜歡這主意的原因是, 除了對控制疾病研究帶來 一個全新層面的領域之外, 通常這種我們想要的人為干預 也就是我們該做的事, 也是大家都非常希望想要的干預. 但是人們還無法判斷其成本是否合理。
So, this is the kind of thing I'm talking about. If we know that we're going to get extra bang for the buck from providing clean water, then I think that we can say, let's push the effort into that aspect of the control, so that we can actually solve the problem, even though, if you just look at the frequency of infection, you would suggest that you can't solve the problem well enough just by cleaning up water supply. Anyhow, I'll end that there, and thank you very much.
因此,這也是我想提的. 如果我們知道提供清潔的水源,我們會得到額外的好處. 那麼我認為我們會說 讓我們努力推廣這方面的的控制, 這樣我們就能真正解決問題. 即使當你仔細研究傳染病的發生率時, 你或許會說僅靠清潔水源無法 完全解決問題,但也值得去實行. 好!我就講到此,非常感謝大家.
(Applause)
拍手!